In experimental animals, both thyroid hormone deprivation and prenatal hypothyroidism are reported to influence importantly the biochemical and morphological development of the sympathetic nervous system (SNS). To date, nothing is known at the cellular and molecular levels about the mechanism(s) by which thyroid hormones exert these effects. The aims of the present proposal are to determine the critical time period for the action of thyroid hormones on SNS development and to identify the loci of the thyroid hormone actions responsible for this development. Finally, the independent or integrated mechanism(s) of thyroid hormone and nerve growth factor action will be studied during ontogenetic development of the SNS. Nerve growth factor is known to be indispensible for growth and maturation of sympathetic noradrenergic neurons of the autonomic nervous system during early stages of their development and for the maintenance of the differentiated state of these autonomic neurons throughout their life span. Our approach will include studies in mice with experimentally induced hypothyroidism as well as mutant mice with genetic hypothyroidism. The mouse superior cervical ganglion (SCG) will be used as the model for these studies of SNS development.